The important roles of the lower urinary tract are urine storage and voiding, which are regulated by a coordinated action of the bladder and the urethra. That is, during urine storage, the bladder smooth muscle is relaxed and the urethral sphincter is contracted, whereby a state in which urethral resistance is high is maintained and urinary continence is maintained. On the other hand, during voiding, the bladder smooth muscle is contracted, the urethra smooth muscle is relaxed, and contraction of the external urethral sphincter is also inhibited. Examples of the lower urinary tract disorder include urine storage dysfunction such as overactive bladder, in which urine cannot be retained during urine storage, and voiding dysfunction, in which urine cannot be drained sufficiently during voiding due to an increase in the urethral resistance or a decrease in the bladder contractile force. These two disorders may develop simultaneously in some cases.
Voiding dysfunction is caused by a decrease in the bladder contractile force or an increase in urethral resistance during voiding, and causes difficulty in voiding, straining during voiding, a weak urine stream, extension of voiding time, an increase in residual urine, a decrease in voiding efficiency, or the like. The decrease in the bladder contractile force during voiding is referred to as underactive bladder, acontractile bladder, or the like. As a factor causing such a decrease in the bladder contractile force during voiding, for example, aging, diabetes mellitus, benign prostatic hyperplasia, neurological diseases such as Parkinson's disease and multiple sclerosis, spinal cord injury, neurological disorders by pelvic surgery, and the like have been known (Reviews in Urology, 15: pp. 11-22 (2013)).
As a mechanism to cause bladder contraction during voiding, involvement of muscarinic receptor stimulation has been known. That is, during urination, the pelvic nerve which is a parasympathetic nerve governing the bladder is excited to release acetylcholine from nerve terminals. The released acetylcholine binds to a muscarinic receptor present in the bladder smooth muscle to cause contraction of the bladder smooth muscle (Journal of Pharmacological Sciences, 112: pp. 121-127 (2010)). The muscarinic receptors are currently classified into five subtypes, M1, M2, M3, M4, and M5, and it has been known that the subtypes involving the contraction in the bladder smooth muscle is mainly M3 (Pharmacological Reviews, 50: pp. 279-290 (1998); The Journal of Neuroscience, 22: pp. 10627-10632 (2002)).
As a therapeutic drug for a decrease in bladder contractile force during voiding, bethanechol chloride which is a non-selective muscarinic receptor agonist and distigmine bromide which is a cholinesterase inhibitor have been known. However, it has been known that these drugs have cholinergic side effects such as diarrhea, abdominal pain, and perspiration. In addition, there may be cases where cholinergic crisis is occurred as a serious side effect, which require attention during use (Ubretid (registered trademark), tablet 5 mg, package insert, Torii Pharmaceutical Co., Ltd., and Besacholine (registered trademark) powder 5%, package insert, Eisai Co., Ltd.).
On the other hand, as a cause of an increase in urethral resistance, voiding dysfunction associated with benign prostatic hyperplasia has been well-known, which is characterized in that the urethra is partially occluded by nodular enlargement of the prostatic tissue. Currently, an adrenergic a, receptor antagonist has been used as a therapeutic drug for voiding dysfunction associated with benign prostatic hyperplasia (Pharmacology, 65: pp. 119-128 (2002)). On the other hand, the effectiveness of the adrenaline α1 receptor antagonist for voiding dysfunction that is not associated with benign prostatic hyperplasia is unclear, as compared with the effectiveness against voiding dysfunction that is associated with benign prostatic hyperplasia (Journal of Pharmacological Sciences, 112: pp. 121-127 (2010)).
Furthermore, for voiding dysfunction caused by a decrease in bladder contractile force or an increase in urethral resistance, residual urine after voiding may be observed in some cases. The increased residual urine may cause a decrease in effective bladder capacity, and thus cause overactive bladder symptoms such as urinary frequency or severe symptoms such as hydronephrosis in some cases.
There has been a demand for a more effective therapeutic drug for such bladder/urethral diseases due to a decrease in the bladder contractile force or an increase in urethral resistance during voiding, or symptoms thereof (Reviews in Urology, 15: pp. 11-22 (2013)).
Patent Document 1 discloses that a compound represented by the following general formula (A) including a compound of the formula (A1) below, which is disclosed in Example 315, has a Ba/F3 cell proliferative activity through a human c-myeloproliferative leukemia virus type P (c-Mpl), and has thrombocyte increasing activity.

(in which R3 represents an aromatic hetero ring which may be substituted, or the like. For the other symbols, refer to the patent publication).
Patent Document 2 discloses that a compound represented by the following general formula (B) has an AMPK pathway activating action.

(in which Ring B represents a heteroarylene or the like, J represents —NR13C(O)— or the like, D1, D2 and D3 each represent N, CH, or the like, E represents —NR1R2 or the like, and R1 and R2 may be combined with an adjacent nitrogen atom to form a heterocycloalkyl which may be substituted. For the other symbols, refer to this publication).
Non-Patent Document 1 discloses that a compound represented by the following formula (C1) is an allosteric enhancer of a muscarinic M3 receptor.

Non-Patent Document 2 discloses that WIN 62,577 represented by the following formula is a rat NK1 receptor antagonist and, at the same time, an allosteric enhancer of a muscarinic receptor.
